1. Technical Field
The invention relates generally to chemically sensitive field effect transducers and like devices. More specifically, the invention relates to a mode of operating such devices without the use of a reference electrode.
2. Description of the Related Art
Chemically sensitive field effect transducers or transistors (CHEMFETs) have been the subject of extensive research and commercial applications in both industrial and medical technology fields. In medical applications in particular, measurement and monitoring of chemical properties such as the presence, activity, and concentration of chemical and biochemical substances such as ions, enzymes, antibodies, antigens, hormones, and reducible gases, are important for proper diagnosis and treatment. In a variety of in vivo and in vitro situations, there is a need for miniaturizing the measuring apparatus, as well as improving the speed and reducing the cost of performing the measurements. The utilization of CHEMFETs is desirable due to their small size and large volume production aspects resulting in reduced cost.
The term "CHEMFET" as used hereinafter designates a device which functionally operates like a conventional insulated-gate field effect transistor (IGFET or MOSFET) but in which the conducting metal gate layer is omitted or replaced with a chemically sensitive region or membrane. One such device is described in U.S. Pat. No. 4,020,830 issued to Johnson et al. and the teachings of that patent are fully incorporated herein by reference. It is common in the art to classify CHEMFETs of the type described by Johnson et al. by the nature of the chemically sensitive system and the substances with which they react. Thus, ion sensitive devices are usually designated "ISFETs" and immunological devices are commonly known as "IMFETs." The present invention is not limited to any particular class of CHEMFET and the use of this term should not be interpreted in a limiting sense. Accordingly, as used herein, "CHEMFET" refers to any device of the generally described type irrespective of the particular chemical system such device is adapted to interface with or other variations such as whether or not they use separate insulator and membrane layers, and so on. The particular structures and methodologies of making CHEMFETs is well known and not considered part of the present invention.
Generally, a CHEMFET is a field effect device functionally analogous to a conventional MOSFET. A semiconductor substrate is formed with source and drain regions separated by a variably conductive channel. In a MOSFET, a gate region overlays the channel and includes an insulator layer such as silicon dioxide and a gate metal contact layer thereon such as aluminum. A CHEMFET, on the other hand, replaces the gate metal contact and/or the gate region insulator layer with a chemically sensitive region or membrane particularly selected and adapted for the substance and chemical properties under test. The conductivity of the channel varies in relation to the interfacial potential between the sensitive region and the substance. Thus, a measurement of the interfacial potential or the channel conductivity corresponds to a measurement of the particular chemical property or activity of interest.
A significant problem with the use of CHEMFETs is the lack of reproducible measurements when monitoring the channel conductivity, as by measuring the source-to-drain current. Thus, it is common practice to use a reference electrode to bias the CHEMFET at a predetermined operating point or to use the reference electrode as a negative Feedback element. This latter technique permits measurement of the interfacial potential, and thus the chemical property of interest. For example, Johnson et al. show the use of a reference electrode with an enhancement mode device to establish a conductive channel, and the potential at the substance/gate membrane interface varies the channel conductance, and hence the measured source-to-drain current. U.S. Pat. No. 4,488,556, issued to Ho, shows a system wherein the gate region of the transducer is maintained at a potential equal to the combination of a reference electrode potential plus the electrochemical potential generated at the membrane/substance interface. With this technique, the use of the reference electrode permits a means for measuring differences in the interfacial potential caused by changes in the chemical properties under test and provides more reproducible measurements, since the interfacial potential exhibits less drift than the corresponding source/drain current.
While the CHEMFET applications known heretofore are useful for their intended purpose, the required reference electrode is an undesirable aspect of such systems. The term "reference electrode" as used herein includes standard nonpolarizable devices for maintaining constant liquid junction potentials, such as standard calomel and silver-silver chloride electrodes, as well as polarizable electrodes such as described in U.S. Pat. No. 4,269,682, issued to Yano et al. A typical reference electrode is unsuitable for in vivo implant applications because of its large size, but when the reference electrode is miniaturized, measurement values become more unstable and unreliable, and the electrode has a shorter useful life.
While some advances have been made in improving the design of the reference electrode. For example see U.S. Pat. No. 4,269,682, supra, it is clear that any application which requires use of a reference electrode to obtain reproducible results will be necessarily and undesirably limited and more costly. It is apparent that the need has long existed for a way to utilize CHEMFETs effectively without a reference electrode.